{"entity":{"id":"idea-moon-irae-prediction-and-prevention","kind":"idea","name":"Predict immune side-effects before they happen and pre-empt them","aka":[],"tldr":"Immunotherapy can trigger dangerous attacks on the gut, lungs or heart. Use blood, gut bacteria and genetic markers to spot who is at risk and act early.","summary":"Immune-related adverse events cause treatment discontinuation and death, and their management is reactive. Autoantibody profiles, HLA types, microbiome composition, baseline cytokines and early T-cell clonal expansion are each associated with specific toxicities in retrospective series. The proposal is a prospective biomarker cohort across checkpoint inhibitor indications to derive and validate a toxicity risk model, followed by trials of pre-emptive strategies (early steroid-sparing agents, microbiome modulation, intensified monitoring) in high-risk patients.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-immunotherapy-response"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A validated model identifies a high-risk group with at least threefold risk of grade 3+ immune toxicity, and pre-emptive management reduces severe events and discontinuations without reducing response rates.","rationale":"Toxicity and efficacy are partially separable; preventive strategies such as prophylactic vedolizumab or IL-6 blockade have early data suggesting response is preserved.","test":"Prospective 3,000-patient cohort with banked samples; then a randomised trial of pre-emptive management in model-defined high-risk patients.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-moon-irae-prediction-and-prevention/","neighbours":{"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"paper":[{"id":"paper-di-maio-j-clin-oncol","kind":"paper","name":"Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials","route":"/key-papers/paper-di-maio-j-clin-oncol/"}]}}